title: Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury.
abstract: BACKGROUND
  Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO2 by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO2 response to INO.
  
  
  METHODS
  After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion.
  
  
  RESULTS
  Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 > or = 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO.
  
  
  CONCLUSIONS
  ET-1 may therefore be involved in mediating the response to INO.
authors.affiliation: Department of Medical Sciences, Clinical Physiology, Uppsala University, S-75185 Uppsala, Sweden.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Trachsel
authors.forename: Ginette
authors.initials: G
authors.lastname: Deby-Dupont
authors.forename: Edwige
authors.initials: E
authors.lastname: Maurenbrecher
authors.forename: Monique
authors.initials: M
authors.lastname: Nys
authors.forename: Maurice
authors.initials: M
authors.lastname: Lamy
authors.forename: Göran
authors.initials: G
authors.lastname: Hedenstierna
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D018836:Inflammation Mediators / Q000097:blood*; D055370:Lung Injury / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D034421:Sus scrofa
chemical_list: D004731:Endotoxins; D018836:Inflammation Mediators; D009569:Nitric Oxide